The blood of humans and other mammals is now known to be rich with a large amount of previously unstudied molecules that could reflect the ongoing physiologic state of various tissues. As blood flows through most of the tissues of the human body, the origins of plasma proteins may be diverse. The complex mixture of a blood plasma proteome from a healthy human individual is expected to comprise well known blood component proteins such as albumin and other known proteins in a relatively high abundance and various other proteins that originate from circulating blood cells.
Bone normally undergoes continuous turnover and remodeling comprising bone formation and bone resorption; two opposite and well balanced processes. A number of proteins related to this normal regenerative process may be found in the plasma and/or urine of healthy individuals in amounts that are generally correlated with a relative decrease or increase in bone turnover activity. See, e.g., Anderson et al., Mol. Cell. Proteomics, 1: 845-867 (2002). Following fracture, a large number of growth factors, cytokines, and their cognate receptors involved in bone repair are highly expressed at the fracture site in the first hours following injury. Skeletal tissues are the main source of such proteins, while some are released from associated inflammatory cells at the site of injury. See, e.g., Barnes et al., J. Bone Miner. Res., 14: 1805-1815 (1999).
Injuries to bones and cartilage are routinely assessed and monitored using such well known standard methods such as X-rays, bone scans, and magnetic resonance imaging (MRI). However, such methods typically require transporting a patient to a location that contains the machinery necessary to carry out such analyses. Yet there are many situations in which it would be advantageous to be able to determine whether a patient has sustained a bone fracture and/or cartilage injury without the need or benefit of X-ray, bone scan, or MRI studies. In addition, injuries to bone and cartilage are not always evident by such methods. Accordingly, needs remain for additional means and methods to detect and assess bone and cartilage injuries in patients.